[PDF][PDF] Tissue-specific signals control reversible program of localization and functional polarization of macrophages

Y Okabe, R Medzhitov - Cell, 2014 - cell.com
Cell, 2014cell.com
Tissue-resident macrophages are highly heterogeneous in terms of their functions and
phenotypes as a consequence of adaptation to different tissue environments. Local tissue-
derived signals are thought to control functional polarization of resident macrophages;
however, the identity of these signals remains largely unknown. It is also unknown whether
functional heterogeneity is a result of irreversible lineage-specific differentiation or a
consequence of continuous but reversible induction of diverse functional programs. Here …
Summary
Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.
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